General Information

Database accession: MF2202001

Name: GTPase binding domain of neural Wiskott-Aldrich syndrome protein in complex with E. coli EspF(U)

PDB ID: 2lnh PDB

Experimental method: NMR

Assembly: heterodimer

Source organism: Homo sapiens / Escherichia coli O157:H7

Primer publication of the structure:

Aitio O, Hellman M, Skehan B, Kesti T, Leong JM, Saksela K, Permi P
Enterohaemorrhagic Escherichia Coli Exploits a Tryptophan Switch to Hijack Host F-Actin Assembly.

(2012) Structure :

PMID: 22921828 PubMed


Intrinsically disordered protein (IDP)-mediated interactions are often characterized by low affinity but high specificity. These traits are essential in signaling and regulation that require reversibility. Enterohaemorrhagic Escherichia coli (EHEC) exploit this situation by commandeering host cytoskeletal signaling to stimulate actin assembly beneath bound bacteria, generating "pedestals" that promote intestinal colonization. EHEC translocates two proteins, EspF(U) and Tir, which form a complex with the host protein IRTKS. The interaction of this complex with N-WASP triggers localized actin polymerization. We show that EspF(U) is an IDP that contains a transiently α-helical N-terminus and dynamic C-terminus. Our structure shows that single EspF(U) repeat forms a high-affinity trimolecular complex with N-WASP and IRTKS. We demonstrate that bacterial and cellular ligands interact with IRTKS SH3 in a similar fashion, but the bacterial protein has evolved to outcompete cellular targets by utilizing a tryptophan switch that offers superior binding affinity enabling EHEC-induced pedestal formation.

Function and Biology Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown.

Molecular function: not assigned

Biological process: not assigned

Cellular component: not assigned

Structure Summary Structural annotations of the participating protein chains.

Entry contents: 2 distinct polypeptide molecules

Chains: A, C

Notes: Chain B was removed as it is ordered and does not directly contribute to the interaction between chains A and C. Chain C was truncated to exclude the region in contact with chain B.

Number of unique protein segments: 2

Chain A

Name: Neural Wiskott-Aldrich syndrome protein

Source organism: Homo sapiens

Length: 65 residues


UniProtKB AC: O00401 (positions: 206-270) UniProt Coverage: 12.9%

UniRef90 AC: UniRef90_O00401 (positions: 207-270) UniRef90

Chain C

Name: Secreted effector protein EspF(U)

Source organism: Escherichia coli O157:H7

Length: 48 residues


UniProtKB AC: P0DJ89 (positions: 220-267) UniProt Coverage: 14.2%

UniRef90 AC: UniRef90_P0DJ88 (positions: 221-267) UniRef90

Evidence Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding.

Chain A:

A close homologue sharing the same Pfam domain (PF00786.25) has been experimentally characterized as disordered in DisProt entry DP00215 and IDEAL entry IID00269.

Chain C:

The 221-314 region described in IDEAL entry IID90008 covers 97.9% of the sequence present in the structure. The interacting region has also been shown to be disordered in the structure's source publication (PMID: 22921828).

Related Structure(s) Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap).

No related structure was found in the Protein Data Bank.

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